Heart failure is a debilitating disease in which abnormal function of the heart leads to inadequate blood flow to fulfill the needs of the tissues and organs of the body. Typically, the heart loses propulsive power because the cardiac muscle loses capacity to stretch and contract. Often, the ventricles do not adequately fill with blood between heartbeats and the valves regulating blood flow become leaky, allowing regurgitation or back-flow of blood. The impairment of arterial circulation deprives vital organs of oxygen and nutrients. Fatigue, weakness and the inability to carry out daily tasks may result. Not all heart failure patients suffer debilitating symptoms immediately. Some may live actively for years. Yet, with few exceptions, the disease is relentlessly progressive. As heart failure progresses, it tends to become increasingly difficult to manage. Even the compensatory responses it triggers in the body may themselves eventually complicate the clinical prognosis. For example, when the heart attempts to compensate for reduced cardiac output, it adds cardiac muscle causing the ventricles to grow in volume in an attempt to pump more blood with each heartbeat, i.e. to increase the stroke volume. This places a still higher demand on the heart's oxygen supply. If the oxygen supply falls short of the growing demand, as it often does, further injury to the heart may result, typically in the form of myocardial ischemia or myocardial infarction. The additional muscle mass may also stiffen the heart walls to hamper rather than assist in providing cardiac output. A particularly severe form of heart failure is congestive heart failure (CHF) wherein the weak pumping of the heart leads to build-up of fluids in the lungs and other organs and tissues.
CRT is a form of therapy that seeks to normalize asynchronous cardiac electrical activation and the resultant asynchronous contractions within heart failure patients by delivering synchronized pacing stimulus to the ventricles. The pacing stimulus is typically synchronized so as to help to improve cardiac contractility and hence mitigate CHF. CRT and related therapies are discussed in, for example, U.S. Pat. No. 6,643,546 to Mathis et al., entitled “Multi-Electrode Apparatus and Method for Treatment Of Congestive Heart Failure”; U.S. Pat. No. 6,628,988 to Kramer et al., entitled “Apparatus and Method for Reversal Of Myocardial Remodeling With Electrical Stimulation”; and U.S. Pat. No. 6,512,952 to Stahmann et al., entitled “Method And Apparatus for Maintaining Synchronized Pacing.” See, also, U.S. Patent Application No. 2008/0306567 of Park et al., entitled “System and Method for Improving CRT Response and Identifying Potential Non-Responders to CRT Therapy” and U.S. Patent Application No. 2007/0179390 of Schecter, entitled “Global Cardiac Performance.”
Insofar as contractility is concerned, it is well known that due to its larger muscle mass and pressure development, the contractility of the left ventricle of the human heart is significantly higher than that of the right. Even with this disparity between right and left contractility, muscle wraps from the left ventricle enveloping the right ventricle provide a boost in effort to the right ventricle, thereby producing a functional equilibrium of cardiac output from the two ventricles. In some forms of CHF, the contractility of both ventricles fails, such as with idiopathic dilated cardiomyopathy. In other cases, one ventricle is independently depressed due to an ischemia that causes loss of musculature. In the latter case, a functional disequilibrium between the pumping of the ventricles develops, for example, when the left ventricular contractility becomes depressed toward the values of the right ventricle or even lower.
As noted, CRT may be used to mitigate CHF. Unfortunately, not all patients with CHF respond to CRT. In particular, patients without a wide QRS complex are not considered for CRT as these patients are deemed to be “non-responders.” CRT therapy is deemed ineffective in these patients because the relatively narrow QRS may be indicative of a left-to-right contractility disequilibrium caused by the weakening of one of the ventricles and that disequilibrium remains even with proper CRT activation timing. Hence, it would be advantageous for the next generation of implantable medical devices to treat these CRT non-responders and other CRT non-candidates in an effort to restore the normal contractility state of the heart. In doing so, the entire heart muscle would approach its available peak efficiency.
One possible technique for extending CRT to nonresponders is to exploit post-extrasystolic potentiation (PESP). PESP is a physiological phenomenon whereby a premature cardiac activation will produce an ineffective beat but will then potentiate the mechanical activity of the subsequent beat. This potentiation is evidenced by increases in stroke volume, stroke work, systolic blood pressure and cardiac contractility. In brief, it is believed that the potentiation is due to an increase of calcium ions released into the sarcoplasmic reticulum that cause a greater cross-linking of actin and myosin filaments. The extrasystole also produces a compensatory pause that causes the subsequent beat to occur later than would be expected, slowing the heart rate.
Thus PESP may be used to enhance CRT by increasing contractility beyond what is typically achieved by merely restoring synchrony. Also, PESP may be used to slow the ventricles during atrial fibrillation (AF) because PESP tends to prolong the refractory interval. That is, the additional depolarization during a relative refractory period caused by the PESP pulse has the effect of extending the overall refractory interval. The longer refractory interval acts to block the conduction of rapid atrial impulses associated with AF. PESP thus can provide for rate control during AF. Further, PESP may be used to treat patients with low ejection fraction (EF) and narrow QRS heart failure, i.e. a form of heart failure where the electrical signals associated with ventricular depolarization (QRS complexes) are shorter than usual. PESP may also be used to treat cardiac insufficiency. Still further, PESP may be used to treat heart failure with preserved EF. Patients with heart failure with preserved EF can benefit because PESP enhances the rate of relaxation. PESP therapy and related techniques are discussed in: U.S. Pat. Nos. 7,184,833; 7,289,850; U.S. Patent Application 2007/0250122; U.S. Patent Application 2006/0149184; and U.S. Patent Application 2006/0247698.
FIG. 1 illustrates the effects of PESP. A first pair of traces illustrate a normal sinus rhythm (i.e. no PESP) by way of an electrocardiogram (ECG) 2 and a ventricular pressure graph 4. A first intrinsic depolarization 6 within the ECG causes the ventricles to contract, resulting in an increase in ventricular pressure 8. Each subsequent depolarization 6 triggers an increase in ventricular pressure 8 of about equal magnitude. In contrast, a second pair of traces 10 and 12 illustrate the effects of PESP. ECG 10 shows an initial depolarization 14 followed shortly thereafter by an extrasystolic pulse 16. The initial depolarization 14 triggers a contraction that causes an increase in ventricular pressure 18, as with normal sinus rhythm. The extrasystolic pulse 16 triggers an ineffective contraction that results a minimal increase in ventricular pressure 20. This is an ineffective beat that results in a compensatory pause before a next intrinsic depolarization, i.e. the next heartbeat is delayed. The ineffective beat also triggers PESP, which has the effect of potentiating the next beat. That is, the next intrinsic depolarization 22 triggers a stronger contraction that results in a much larger magnitude increase in ventricular pressure 24. This stronger contraction is due to the potentiation achieved via PESP. Note, though, that the potentiation achieved via PESP can degrade rapidly on subsequent beats due to the reuptake of extra calcium during the compensatory pause, resulting in less potentiation of subsequent beats.
To counter the degradation and maintain potentiation, continuous PESP techniques have been developed that exploit either coupled pacing or paired pacing. With coupled pacing, the implantable device senses a ventricular activation and paces at a particular coupling interval set to maintain potentiation at a consistent level. This is illustrated by way of traces 26 and 28 of FIG. 2. Each intrinsic depolarization 30 is followed by an extrasystolic pulse 32 (subject to a coupling interval), which triggers a potentiated contraction 34 with greater magnitude than unpotentiated contractions such as initial contraction 36. By continuously applying extrasystolic pulses subject to a suitable coupling interval, the resulting potentiation is maintained at more or less uniform levels. However, the lengthy compensatory pause following each extrasystolic pulse can result in a significant reduction in overall heart rate (sometimes reducing it by half), which may have the effect of reducing overall cardiac output and hence counteracting some or all of the benefits achieved by the potentiation. Hence, although coupled pacing can avoid the degradation of potentiation occurring with non-continuous PESP, the sharp reduction in heart rate is problematic, at least within some patients.
Paired pacing can be used to avoid degradation of potentiation while also avoiding the sharp drop in heart rate. Within FIG. 2, paired pacing is shown by way of traces 36 and 38. Pacing pulses are delivered at a rate high enough so that intrinsic depolarizations do not occur. The pacing pulses are delivered in pairs. A first pulse 40 of each pair triggers a corresponding contraction of the ventricles such as initial contraction 41. The second pulse 42 of each pair (delivered subject to an interpulse interval) then triggers PESP so as to potentiate subsequent contractions 44 to have a greater magnitude than unpotentiated contractions (e.g. initial contraction 41.) By continuously applying extrasystolic pulses subject to a suitable interpulse interval, the resulting potentiation is maintained at more or less uniform levels. Moreover, since the heart is paced to avoid intrinsic depolarization, the lengthy compensatory pause occurring with coupled pacing is avoided and hence elevated cardiac output can be maintained.
Paired and coupled pacing techniques are discussed in U.S. Published Patent Application No. 2010/0094371 of Bornzin et al., entitled “Systems and Methods for Paired/Coupled Pacing” and in U.S. patent application Ser. No. 11/929,719, also of Bornzin et al., filed Oct. 30, 2007, entitled “Systems and Methods for Paired/Coupled Pacing and Dynamic Overdrive/Underdrive Pacing.” See, also, U.S. patent application Ser. No. 13/196,763, of Koh, filed Aug. 2, 2011, entitled “Systems and Methods for Controlling Paired Pacing based on Patient Activity for use with an Implantable Medical Device.”
Despite the apparent advantages of continuous PESP—especially paired pacing—such techniques have sometimes met with resistance within the cardiac pacing community. One possible reason is that, as conventionally envisioned, paired pacing is applied only at a single site, such as a single site in the RV, or is applied by equal amounts in the LV and RV. As already noted, though, the contractility of one ventricle might be independently depressed due to loss of musculature because of an ischemic event. As such, a functional disequilibrium may develop between the weakened ventricle and the intact ventricle. Single-site PESP would do little or nothing to rebalance the two ventricles. Likewise, applying the same level of PESP to both the LV and RV where only one has been weakened would likely maintain the disequilibrium, and may even make it worse in some cases.
Accordingly, it would be desirable to provide improved techniques for controlling paired PESP that address these and other problems and it is to this end that aspects of the invention are generally directed. In particular, it is desirable to provide paired PESP techniques that would serve to rebalance RV and LV contractilities in cases where one ventricle is weakened and the other is intact. By successfully rebalancing the right and left contractilities, the entire heart muscle would approach its available peak efficiency. Moreover, a rebalancing of left and right contractility would allow CRT to be applied to at least some patients who are conventionally regarded as non-responders due to contractility disequilibrium.